Polysilsesquioxane nanoparticles for triggered release of cisplatin and effective cancer chemoradiotherapy

Chemoradiotherapy is a well-established treatment paradigm in oncology. There has been strong interest in identifying strategies to further improve its therapeutic index. An innovative strategy is to utilize nanoparticle (NP) chemotherapeutics in chemoradiation. Since the most commonly utilized chemotherapeutic with radiotherapy is cisplatin, the development of an NP cisplatin for chemoradiotherapy has the highest potential impact on this treatment. Here, we report the development of an NP comprised of polysilsesquioxane (PSQ) polymer crosslinked by a cisplatin prodrug (Cisplatin-PSQ) and its utilization in chemoradiotherapy using non-small cell lung cancer as a disease model. Cisplatin-PSQ NP has an exceptionally high loading of cisplatin. Cisplatin-PSQ NPs were evaluated in chemoradiotherapy in vitro and in vivo. They demonstrated significantly higher therapeutic efficacy when compared to cisplatin. These results suggest that the Cisplatin-PSQ NP holds potential for clinical translation in chemoradiotherapy.From the Clinical EditorThese authors present an innovative strategy utilizing the presence of platinum in nanoparticle chemotherapeutics for chemoradiation, demonstrating its efficacy in a non-small cell lung cancer model.

Graphical AbstractCisplatin is the most commonly utilized chemotherapeutic in chemoradiotherapy for cancer. Because of its importance, there has been strong interest in identifying strategies to further improve the therapeutic index of cisplatin-based chemoradiotherapy. One approach is to develop and utilize nanoparticle cisplatin. In this study, we engineered a novel nanoparticle cisplatin (Cisplatin-PSQ NP). Cisplatin-PSQ NP has an exceptionally high loading of cisplatin. We demonstrated that Cisplatin-PSQ NP is more effective than small molecule cisplatin using mouse models of non-small cell lung cancer. Our results suggest that Cisplatin-PSQ NP holds high potential to further improve cancer chemoradiotherapy.Figure optionsDownload high-quality image (104 K)Download as PowerPoint slide